1. Field of the Invention
This invention relates to a laminated rubber stopper, in particular, a laminated rubber stopper used for sealing vials, specifically, vessels for medicaments, medical vessels, instruments, etc. (which will hereinafter be referred to as xe2x80x9ca laminated rubber stopper for a medicament vialxe2x80x9d).
2. Description of the Prior Art
For a stopper material of a medicament vessel, medical vessel, instrument, etc., it is required to have heat resistance, compression strain resistance, enriched softness, chemical inertness and low permeability to gases or water. In respect of the sealing property, in particular, rubbers are excellent and there have been used natural rubbers from olden times and synthetic rubbers of late, for example, isobutylenes, isoprene copolymer rubbers (IIR), etc. having been recommended from the sanitary point of view. When using these rubbers, however, there arise problems that vulcanizers, compounding agents, etc. contained in the rubbers dissolve in medicaments held in vessels, vessel contents adsorb on rubber surfaces and contamination takes place due to fine particles from the rubber materials during production steps or storage of medicaments.
As described above, the rubber stopper used with a vessel for an injection to give an important function for maintaining stability of the injection is generally in a coated form with a thermoplastic olefinic resin such as polypropylene or polyethylene or a fluoro resin, in such a manner that a part or whole part of the surface area to be contacted with the injection is laminated, so as to prevent the rubber stopper from dissolving or evaporating of compounding chemicals or vulcanizing reaction products in the injection.
For example, JP-A-60-251041 discloses a laminated rubber stopper using a fluoro resin with a specified composition, JP-A-63-296756 discloses both surfaces-laminated rubber stopper for medicaments, in which a part or whole part of the lower surface and the upper surface are laminated with a fluoro resin, JP-A-2-136139 discloses a rubber stopper for a medical container, in which a soft fluoro resin with a specified composition is laminated and JP-A-59-005046 discloses a laminated rubber stopper for a medicament, in which the whole of the lower surface is laminated with a specified fluoro resin, and a process for the production of the same.
In addition, U.S. Pat. No. 4,554,125 discloses a laminated rubber stopper for a medicament, in which the whole lower surface is laminated with soft polypropylene resin, JP-A-3-140231 and U.S. Pat. No. 5,527,580 disclose a laminated rubber stopper for a vial, in which a part or whole part of the lower surface is laminated with polyethylene resin having a limited molecular weight, and further, a process for the production of the same is disclosed in JP-A-3-270928. Rubber stoppers for medicaments, having various forms, obtained by the prior art, have different quality and function, depending on the quality of the laminated film and the laminated site, in combination.
In particular, an invention described in the above described JP-A-59-005046 relates to a rubber stopper comprising a synthetic rubber whose lower surface is fully laminated with a film of a fluorine-containing copolymer and a process for the production of the same, the copolymer being selected from FEP, PEA, ETFE, etc.
However, the quality and function required for a rubber stopper for an injection include sealing property, medicament adaptability (role for mainly maintaining stability of a content medicament for a long time), self-closing property, resistance to fragmentation (also referred to as fragment resistance), sterilization adaptability and many other physicochemical properties. In an injection of a lately developed, new type, above all, a number of improving efforts of the physicochemical properties of a rubber stopper as to protecting the medicament from contamination due to rubber compounding components have been made for the purpose of the medicament stability related with antioxidation property, sealing property for protecting from bacteria contamination and deterioration or potency lowering of micro amount components, but in fact, sufficient results have not been obtained yet.
Under the situation, in the practice of the prior art, for example, a rubber stopper having a fluoro resin film laminated on the lower surface of the rubber stopper, there are obtained excellent effects in medicament stability, but such a problem has arised that the sealing degree is largely dispersed by influences of the dimensional precision (roughness of upper surface of vial mouth part or inner diameter thereof).
The inventors have made various efforts to solve the above described problems and consequently have found that the fluoro resin has more excellent barrier effect of permeation (barrier property) than other thermoplastic resins and in addition, the sealing property of a rubber stopper can be obtained by selecting a fluoro resin having a small flexural modulus, to be laminated, and lower friction resistance with the upper surface of the vial mouth part. The present invention is based on this finding.
It is an object of the present invention to provide a laminated rubber stopper for a medicament vial, whereby the above described problems can be resolved.
It is another object of the present invention to provide a laminated rubber stopper for a medicament vial, in which a surface of the rubber body is laminated with a PTFE film, whereby more sufficient and excellent sealing property and barrier effect of permeation as compared with thermoplastic resin film of the prior art can be given.
These objects can be attained by a laminated rubber stopper for a medicament vial, in which the whole lower surface or the whole lower surface and a part of the upper surface of the rubber body is laminated with a thermoplastic film having a flexural modulus in a range of at most 600 MPa and a coefficient of kinetic friction in a range of at most 0.4.